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BMJ Open Nov 2019Smoking in people with serious mental illness is a major public health problem and contributes to significant levels of morbidity and mortality. The aim of the review... (Meta-Analysis)
Meta-Analysis
Pharmacological and behavioural interventions to promote smoking cessation in adults with schizophrenia and bipolar disorders: a systematic review and meta-analysis of randomised trials.
OBJECTIVE
Smoking in people with serious mental illness is a major public health problem and contributes to significant levels of morbidity and mortality. The aim of the review was to systematically examine the efficacy of methods used to aid smoking cessation in people with serious mental illness.
METHOD
A systematic review and meta-analysis of randomised controlled trials to compare the effectiveness and safety of pharmacological and behavioural programmes for smoking cessation in people with serious mental illness. Electronic databases were searched for trials to July 2018. We used the Cochrane Collaboration's tool for assessing the risk of bias.
RESULTS
Twenty-eight randomised controlled trials were identified. Varenicline increased the likelihood of smoking cessation at both 3 months (risk ratio (RR) 3.56, 95% CI 1.82 to 6.96, p=0.0002) and at 6 months (RR 3.69, 95% CI 1.08 to 12.60, p=0.04). Bupropion was effective at 3 months (RR 3.96, 95% CI 1.86 to 8.40, p=0.0003), especially at a dose of 300 mg/day, but there was no evidence of effect at 6 months (RR 2.22, 95% CI 0.52 to 9.47, p=0.28). In one small study, nicotine therapy proved effective at increasing smoking cessation up to a period of 3 months. Bupropion used in conjunction with nicotine replacement therapy showed more effect than single use. Behavioural and bespoke interventions showed little overall benefit. Side effects were found to be low.
CONCLUSION
The new information of this review was the effectiveness of varenicline for smoking cessation at both 3 and 6 months and the lack of evidence to support the use of both bupropion and nicotine products for sustained abstinence longer than 3 months. Overall, the review found relatively few studies in this population.
Topics: Adult; Behavior Therapy; Bipolar Disorder; Humans; Randomized Controlled Trials as Topic; Schizophrenia; Smoking Cessation
PubMed: 31784428
DOI: 10.1136/bmjopen-2018-027389 -
The Cochrane Database of Systematic... Oct 2019A number of treatments can help smokers make a successful quit attempt, but many initially successful quitters relapse over time. Several interventions have been... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A number of treatments can help smokers make a successful quit attempt, but many initially successful quitters relapse over time. Several interventions have been proposed to help prevent relapse.
OBJECTIVES
To assess whether specific interventions for relapse prevention reduce the proportion of recent quitters who return to smoking.
SEARCH METHODS
We searched the Cochrane Tobacco Addiction Group trials register, clinicaltrials.gov, and the ICTRP in May 2019 for studies mentioning relapse prevention or maintenance in their title, abstracts, or keywords.
SELECTION CRITERIA
Randomised or quasi-randomised controlled trials of relapse prevention interventions with a minimum follow-up of six months. We included smokers who quit on their own, were undergoing enforced abstinence, or were participating in treatment programmes. We included studies that compared relapse prevention interventions with a no intervention control, or that compared a cessation programme with additional relapse prevention components with a cessation programme alone.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included 81 studies (69,094 participants), five of which are new to this update. We judged 22 studies to be at high risk of bias, 53 to be at unclear risk of bias, and six studies to be at low risk of bias. Fifty studies included abstainers, and 30 studies helped people to quit and then tested treatments to prevent relapse. Twenty-eight studies focused on special populations who were abstinent because of pregnancy (19 studies), hospital admission (six studies), or military service (three studies). Most studies used behavioural interventions that tried to teach people skills to cope with the urge to smoke, or followed up with additional support. Some studies tested extended pharmacotherapy. We focused on results from those studies that randomised abstainers, as these are the best test of relapse prevention interventions. Of the 12 analyses we conducted in abstainers, three pharmacotherapy analyses showed benefits of the intervention: extended varenicline in assisted abstainers (2 studies, n = 1297, risk ratio (RR) 1.23, 95% confidence interval (CI) 1.08 to 1.41, I = 82%; moderate-certainty evidence), rimonabant in assisted abstainers (1 study, RR 1.29, 95% CI 1.08 to 1.55), and nicotine replacement therapy (NRT) in unaided abstainers (2 studies, n = 2261, RR 1.24, 95% Cl 1.04 to 1.47, I = 56%). The remainder of analyses of pharmacotherapies in abstainers had wide confidence intervals consistent with both no effect and a statistically significant effect in favour of the intervention. These included NRT in hospital inpatients (2 studies, n = 1078, RR 1.23, 95% CI 0.94 to 1.60, I = 0%), NRT in assisted abstainers (2 studies, n = 553, RR 1.04, 95% CI 0.77 to 1.40, I = 0%; low-certainty evidence), extended bupropion in assisted abstainers (6 studies, n = 1697, RR 1.15, 95% CI 0.98 to 1.35, I = 0%; moderate-certainty evidence), and bupropion plus NRT (2 studies, n = 243, RR 1.18, 95% CI 0.75 to 1.87, I = 66%; low-certainty evidence). Analyses of behavioural interventions in abstainers did not detect an effect. These included studies in abstinent pregnant and postpartum women at the end of pregnancy (8 studies, n = 1523, RR 1.05, 95% CI 0.99 to 1.11, I = 0%) and at postpartum follow-up (15 studies, n = 4606, RR 1.02, 95% CI 0.94 to 1.09, I = 3%), studies in hospital inpatients (5 studies, n = 1385, RR 1.10, 95% CI 0.82 to 1.47, I = 58%), and studies in assisted abstainers (11 studies, n = 5523, RR 0.98, 95% CI 0.87 to 1.11, I = 52%; moderate-certainty evidence) and unaided abstainers (5 studies, n = 3561, RR 1.06, 95% CI 0.96 to 1.16, I = 1%) from the general population.
AUTHORS' CONCLUSIONS
Behavioural interventions that teach people to recognise situations that are high risk for relapse along with strategies to cope with them provided no worthwhile benefit in preventing relapse in assisted abstainers, although unexplained statistical heterogeneity means we are only moderately certain of this. In people who have successfully quit smoking using pharmacotherapy, there were mixed results regarding extending pharmacotherapy for longer than is standard. Extended treatment with varenicline helped to prevent relapse; evidence for the effect estimate was of moderate certainty, limited by unexplained statistical heterogeneity. Moderate-certainty evidence, limited by imprecision, did not detect a benefit from extended treatment with bupropion, though confidence intervals mean we could not rule out a clinically important benefit at this stage. Low-certainty evidence, limited by imprecision, did not show a benefit of extended treatment with nicotine replacement therapy in preventing relapse in assisted abstainers. More research is needed in this area, especially as the evidence for extended nicotine replacement therapy in unassisted abstainers did suggest a benefit.
Topics: Behavior Therapy; Humans; Nicotinic Agonists; Randomized Controlled Trials as Topic; Secondary Prevention; Smoking Cessation; Tobacco Use Cessation Devices
PubMed: 31684681
DOI: 10.1002/14651858.CD003999.pub6 -
The Cochrane Database of Systematic... Sep 2019The standard way most people are advised to stop smoking is by quitting abruptly on a designated quit day. However, many people who smoke have tried to quit many times...
BACKGROUND
The standard way most people are advised to stop smoking is by quitting abruptly on a designated quit day. However, many people who smoke have tried to quit many times and may like to try an alternative method. Reducing smoking behaviour before quitting could be an alternative approach to cessation. However, before this method can be recommended it is important to ensure that abrupt quitting is not more effective than reducing to quit, and to determine whether there are ways to optimise reduction methods to increase the chances of cessation.
OBJECTIVES
To assess the effect of reduction-to-quit interventions on long-term smoking cessation.
SEARCH METHODS
We searched the Cochrane Tobacco Addiction Group Specialised Register, MEDLINE, Embase and PsycINFO for studies, using the terms: cold turkey, schedul*, cut* down, cut-down, gradual*, abrupt*, fading, reduc*, taper*, controlled smoking and smoking reduction. We also searched trial registries to identify unpublished studies. Date of the most recent search: 29 October 2018.
SELECTION CRITERIA
Randomised controlled trials in which people who smoked were advised to reduce their smoking consumption before quitting smoking altogether in at least one trial arm. This advice could be delivered using self-help materials or behavioural support, and provided alongside smoking cessation pharmacotherapies or not. We excluded trials that did not assess cessation as an outcome, with follow-up of less than six months, where participants spontaneously reduced without being advised to do so, where the goal of reduction was not to quit altogether, or where participants were advised to switch to cigarettes with lower nicotine levels without reducing the amount of cigarettes smoked or the length of time spent smoking. We also excluded trials carried out in pregnant women.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methods. Smoking cessation was measured after at least six months, using the most rigorous definition available, on an intention-to-treat basis. We calculated risk ratios (RRs) and 95% confidence intervals (CIs) for smoking cessation for each study, where possible. We grouped eligible studies according to the type of comparison (no smoking cessation treatment, abrupt quitting interventions, and other reduction-to-quit interventions) and carried out meta-analyses where appropriate, using a Mantel-Haenszel random-effects model. We also extracted data on quit attempts, pre-quit smoking reduction, adverse events (AEs), serious adverse events (SAEs) and nicotine withdrawal symptoms, and meta-analysed these where sufficient data were available.
MAIN RESULTS
We identified 51 trials with 22,509 participants. Most recruited adults from the community using media or local advertising. People enrolled in the studies typically smoked an average of 23 cigarettes a day. We judged 18 of the studies to be at high risk of bias, but restricting the analysis only to the five studies at low or to the 28 studies at unclear risk of bias did not significantly alter results.We identified very low-certainty evidence, limited by risk of bias, inconsistency and imprecision, comparing the effect of reduction-to-quit interventions with no treatment on cessation rates (RR 1.74, 95% CI 0.90 to 3.38; I = 45%; 6 studies, 1599 participants). However, when comparing reduction-to-quit interventions with abrupt quitting (standard care) we found evidence that neither approach resulted in superior quit rates (RR 1. 01, 95% CI 0.87 to 1.17; I = 29%; 22 studies, 9219 participants). We judged this estimate to be of moderate certainty, due to imprecision. Subgroup analysis provided some evidence (P = 0.01, I = 77%) that reduction-to-quit interventions may result in more favourable quit rates than abrupt quitting if varenicline is used as a reduction aid. Our analysis comparing reduction using pharmacotherapy with reduction alone found low-certainty evidence, limited by inconsistency and imprecision, that reduction aided by pharmacotherapy resulted in higher quit rates (RR 1. 68, 95% CI 1.09 to 2.58; I = 78%; 11 studies, 8636 participants). However, a significant subgroup analysis (P < 0.001, I = 80% for subgroup differences) suggests that this may only be true when fast-acting NRT or varenicline are used (both moderate-certainty evidence) and not when nicotine patch, combination NRT or bupropion are used as an aid (all low- or very low-quality evidence). More evidence is likely to change the interpretation of the latter effects.Although there was some evidence from within-study comparisons that behavioural support for reduction to quit resulted in higher quit rates than self-help resources alone, the relative efficacy of various other characteristics of reduction-to-quit interventions investigated through within- and between-study comparisons did not provide any evidence that they enhanced the success of reduction-to-quit interventions. Pre-quit AEs, SAEs and nicotine withdrawal symptoms were measured variably and infrequently across studies. There was some evidence that AEs occurred more frequently in studies that compared reduction using pharmacotherapy versus no pharmacotherapy; however, the AEs reported were mild and usual symptoms associated with NRT use. There was no clear evidence that the number of people reporting SAEs, or changes in withdrawal symptoms, differed between trial arms.
AUTHORS' CONCLUSIONS
There is moderate-certainty evidence that neither reduction-to-quit nor abrupt quitting interventions result in superior long-term quit rates when compared with one another. Evidence comparing the efficacy of reduction-to-quit interventions with no treatment was inconclusive and of low certainty. There is also low-certainty evidence to suggest that reduction-to-quit interventions may be more effective when pharmacotherapy is used as an aid, particularly fast-acting NRT or varenicline (moderate-certainty evidence). Evidence for any adverse effects of reduction-to-quit interventions was sparse, but available data suggested no excess of pre-quit SAEs or withdrawal symptoms. We downgraded the evidence across comparisons due to risk of bias, inconsistency and imprecision. Future research should aim to match any additional components of multicomponent reduction-to-quit interventions across study arms, so that the effect of reduction can be isolated. In particular, well-conducted, adequately-powered studies should focus on investigating the most effective features of reduction-to-quit interventions to maximise cessation rates.
Topics: Bupropion; Humans; Nicotine; Nicotinic Agonists; Randomized Controlled Trials as Topic; Smoking Cessation; Smoking Reduction; Substance Withdrawal Syndrome; Tobacco Use Cessation Devices
PubMed: 31565800
DOI: 10.1002/14651858.CD013183.pub2 -
The Cochrane Database of Systematic... Aug 2019Pharmacological treatments for tobacco dependence, such as nicotine replacement therapy (NRT), have been shown to be safe and effective interventions for smoking...
BACKGROUND
Pharmacological treatments for tobacco dependence, such as nicotine replacement therapy (NRT), have been shown to be safe and effective interventions for smoking cessation. Higher levels of adherence to these medications increase the likelihood of sustained smoking cessation, but many smokers use them at a lower dose and for less time than is optimal. It is important to determine the effectiveness of interventions designed specifically to increase medication adherence. Such interventions may address motivation to use medication, such as influencing beliefs about the value of taking medications, or provide support to overcome problems with maintaining adherence.
OBJECTIVES
To assess the effectiveness of interventions aiming to increase adherence to medications for smoking cessation on medication adherence and smoking abstinence compared with a control group typically receiving standard care.
SEARCH METHODS
We searched the Cochrane Tobacco Addiction Group Specialized Register, and clinical trial registries (ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform) to the 3 September 2018. We also conducted forward and backward citation searches.
SELECTION CRITERIA
Randomised, cluster-randomised or quasi-randomised studies in which adults using active pharmacological treatment for smoking cessation were allocated to an intervention arm where there was a principal focus on increasing adherence to medications for tobacco dependence, or a control arm providing standard care. Dependent on setting, standard care may have comprised minimal support or varying degrees of behavioural support. Included studies used a measure that allowed assessment of the degree of medication adherence.
DATA COLLECTION AND ANALYSIS
Two authors independently screened studies for eligibility, extracted data for included studies and assessed risk of bias. For continuous outcome measures, we calculated effect sizes as standardised mean differences (SMDs). For dichotomous outcome measures, we calculated effect sizes as risk ratios (RRs). In meta-analyses for adherence outcomes, we combined dichotomous and continuous data using the generic inverse variance method and reported pooled effect sizes as SMDs; for abstinence outcomes, we reported and pooled dichotomous outcomes. We obtained pooled effect sizes with 95% confidence intervals (CIs) using random-effects models. We conducted subgroup analyses to assess whether the primary focus of the adherence treatment ('practicalities' versus 'perceptions' versus both), the delivery approach (participant versus clinician-centred) or the medication type were associated with effectiveness.
MAIN RESULTS
We identified two new studies, giving a total of 10 studies, involving 3655 participants. The medication adherence interventions studied were all provided in addition to standard behavioural support.They typically provided further information on the rationale for, and emphasised the importance of, adherence to medication or supported the development of strategies to overcome problems with maintaining adherence (or both). Seven studies targeted adherence to NRT, two to bupropion and one to varenicline. Most studies were judged to be at high or unclear risk of bias, with four of these studies judged at high risk of attrition or detection bias. Only one study was judged to be at low risk of bias.Meta-analysis of all 10 included studies (12 comparisons) provided moderate-certainty evidence that adherence interventions led to small improvements in adherence (i.e. the mean amount of medication consumed; SMD 0.10, 95% CI 0.03 to 0.18; I² = 6%; n = 3655), limited by risk of bias. Subgroup analyses for the primary outcome identified no significant subgroup effects, with effect sizes for subgroups imprecisely estimated. However, there was a very weak indication that interventions focused on the 'practicalities' of adhering to treatment (i.e. capabilities, resources, levels of support or skills) may be effective (SMD 0.21, 95% CI 0.03 to 0.38; I² = 39%; n = 1752), whereas interventions focused on treatment 'perceptions' (i.e. beliefs, cognitions, concerns and preferences; SMD 0.10, 95% CI -0.03 to 0.24; I² = 0%; n = 839) or on both (SMD 0.04, 95% CI -0.08 to 0.16; I² = 0%; n = 1064), may not be effective. Participant-centred interventions may be effective (SMD 0.12, 95% CI 0.02 to 0.23; I² = 20%; n = 2791), whereas those that are clinician-centred may not (SMD 0.09, 95% CI -0.05 to 0.23; I² = 0%; n = 864).Five studies assessed short-term smoking abstinence (five comparisons), while an overlapping set of five studies (seven comparisons) assessed long-term smoking abstinence of six months or more. Meta-analyses resulted in low-certainty evidence that adherence interventions may slightly increase short-term smoking cessation rates (RR 1.08, 95% CI 0.96 to 1.21; I² = 0%; n = 1795) and long-term smoking cessation rates (RR 1.16, 95% CI 0.96 to 1.40; I² = 48%; n = 3593). In both cases, the evidence was limited by risk of bias and imprecision, with CIs encompassing minimal harm as well as moderate benefit, and a high likelihood that further evidence will change the estimate of the effect. There was no evidence that interventions to increase adherence to medication led to any adverse events. Studies did not report on factors plausibly associated with increases in adherence, such as self-efficacy, understanding of and attitudes toward treatment, and motivation and intentions to quit.
AUTHORS' CONCLUSIONS
In people who are stopping smoking and receiving behavioural support, there is moderate-certainty evidence that enhanced behavioural support focusing on adherence to smoking cessation medications can modestly improve adherence. There is only low-certainty evidence that this may slightly improve the likelihood of cessation in the shorter or longer-term. Interventions to increase adherence can aim to address the practicalities of taking medication, change perceptions about medication, such as reasons to take it or concerns about doing so, or both. However, there is currently insufficient evidence to confirm which approach is more effective. There is no evidence on whether such interventions are effective for people who are stopping smoking without standard behavioural support.
Topics: Benzazepines; Bupropion; Drug Therapy, Combination; Humans; Medication Adherence; Nicotinic Agonists; Nortriptyline; Quinoxalines; Randomized Controlled Trials as Topic; Smoking Cessation; Smoking Prevention; Tobacco Use Cessation Devices; Tobacco Use Disorder
PubMed: 31425618
DOI: 10.1002/14651858.CD009164.pub3 -
Nicotine & Tobacco Research : Official... Aug 2019Pharmacogenomic studies have used genetic variants to identify smokers likely to respond to pharmacological treatments for smoking cessation. (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Pharmacogenomic studies have used genetic variants to identify smokers likely to respond to pharmacological treatments for smoking cessation.
METHODS
We performed a systematic review and meta-analysis of primary and secondary analyses of trials of smoking cessation pharmacotherapies. Eligible were trials with data on a priori selected single nucleotide polymorphisms, replicated non-single nucleotide polymorphisms, and/or the nicotine metabolite ratio. We estimated the genotype × treatment interaction as the ratio of risk ratios (RRR) for treatment effects across genotype groups.
RESULTS
We identified 18 trials (N = 9017 participants), including 40 active (bupropion, nicotine replacement therapy [NRT], varenicline, or combination therapies) versus placebo comparisons and 16 active versus active comparisons. There was statistical evidence of heterogeneity across rs16969968 genotypes in CHRNA5 with regard to both 6-month abstinence and end-of-treatment abstinence in non-Hispanic black smokers and end-of-treatment abstinence in non-Hispanic white smokers. There was also heterogeneity across rs1051730 genotypes in CHRNA3 with regard to end-of-treatment abstinence in non-Hispanic white smokers. There was no clear statistical evidence for other genotype-by-treatment combinations. Compared with placebo, NRT was more effective among non-Hispanic black smokers with rs16969968-GG with regard to both 6-month abstinence (RRR for GG vs. GA or AA, 3.51; 95% confidence interval [CI] = 1.19 to 10.30) and end-of-treatment abstinence (RRR for GG vs. GA or AA, 5.84; 95% CI = 1.89 to 18.10). Among non-Hispanic white smokers, NRT effectiveness relative to placebo was comparable across rs1051730 and rs169969960 genotypes.
CONCLUSIONS
We did not identify widespread differential effects of smoking cessation pharmacotherapies based on genotype. The quality of the evidence is generally moderate.
IMPLICATIONS
Although we identified some evidence of genotype × treatment interactions, the vast majority of analyses did not provide evidence of differential treatment response by genotype. Where we find some evidence, these results should be considered preliminary and interpreted with caution because of the small number of contributing trials per genotype comparison, the wide confidence intervals, and the moderate quality of evidence. Prospective trials and individual-patient data meta-analyses accounting for heterogeneity of treatment effects through modeling are needed to assess the clinical utility of genetically informed biomarkers to guide pharmacotherapy choice for smoking cessation.
Topics: Bupropion; Clinical Trials as Topic; Female; Genetic Markers; Genotype; Humans; Male; Polymorphism, Single Nucleotide; Prospective Studies; Smoking; Smoking Cessation; Smoking Cessation Agents; Tobacco Use Cessation Devices; Varenicline
PubMed: 30690475
DOI: 10.1093/ntr/ntz009